Risk factors for opioid toxicity requiring naloxone rescue in adults: a case-control study

Opioid-induced sedation and respiratory depression (OSRD) is a potentially life-threatening side effect of opioid analgesia. However, little is known about the individual and clinical-related factors associated with OSRD in the New Zealand context.

To identify risk factors for OSRD in patients admitted to a large regional health board in New Zealand-Auckland District Health Board (ADHB).

A retrospective matched case-control study design was undertaken among adults who were admitted to ADHB and prescribed opioids in hospital between August 2015 and April 2020. Those who were prescribed opioids and received naloxone for OSRD were defined as cases, whereas those who received opioids but did not experience OSRD were identified as controls. Cases and controls were matched on a 1:1 basis by age (± 10 years). Data were retrieved from the electronic medical records of ADHB. A conditional logistic regression model was used to identify the risk factors for OSRD.

We identified 51 cases, and these were matched with 51 control patients. The odds of experiencing OSRD were four times higher among opioid-naïve patients compared to those exposed to opioids prior to hospital admission (OR  4.113; 95% CI 1.14-14.89). Increased risk of OSRD was also associated with higher serum creatinine level prior to OSRD episode (OR 1.015; 95% CI 1.01-1.03) and a higher oral morphine milligram equivalent (OME) (OR 1.023; 95% CI 1.01-1.04).

Increased risk of OSRD was associated with a higher OME, a higher serum creatinine level prior to OSRD episode, and opioid naivety. Our findings can inform policies that aim to prevent serious adverse effects related to opioids.